Profiling of cyclic hexadepsipeptides roseotoxins synthesized in vitro and in vivo: a combined tandem mass spectrometry and quantum chemical study.

High-performance liquid chromatography and tandem mass spectrometry (HPLC/MS/MS) was used for the detection of cyclic hexadepsipeptides roseotoxins produced by Trichothecium roseum. Roseotoxins were found in both submerged standard cultivation on CzapekDox medium and in vivo cultivation extract obtained from an apple. Roseotoxin chromatographic profiles from these two experiments were compared.

Synthesis of chitooligomer-based glycoconjugates and their binding to the rat natural killer cell activation receptor NKR-P1.

NKR-P1 protein is an important activating receptor at the surface of the rat natural killer cells. GlcNAc and chitooligomers were identified as strong activation ligands in vitro and in vivo. Their clustering brings about increase of their affinity to the NKR-P1 by 3-6 orders.

Synthesis and biological activity of olomoucine II.

Based on our previous experiences with synthesis of purines, novel 2,6,9-trisubstituted purine derivatives were prepared and assayed for the ability to inhibit CDK1/cyclin B kinase. One of newly synthesized compounds designated as olomoucine II, 6-[(2-hydroxybenzyl)amino]-2-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpurine, displays 10 times higher inhibitory activity than roscovitine, potent and specific CDK1 inhibitor. Olomoucine II in vitro cytotoxic activity exceeds purvalanol A, the most potent CDK inhibitor, as it kills the CEM cells with IC(50) value of 3.

Role of amino acid N-methylation in cyclosporins on ring opening and fragmentation mechanisms during collisionally induced dissociation in an ion trap.

The product ion mass spectra (collisionally induced dissociation mass spectra) of 12 different cyclosporins modified at every N-methylated amino acid residue with respect to cyclosporin A were compared and the effect of N-demethylation on ring opening mechanisms was evaluated. The four preferential protonation sites were identified in [MeBmt(1)]-cyclosporins. Three sites represented the N-methylated nitrogens of Sar(3), MeLeu(6) and MeLeu(9), while the remaining one represented the lactone group formed by the intramolecular N,O-acyl shift.

[Tricyclic antidepressants as inhibitors of brain glutathione-S-transferase].

Tricyclic antidepressants, amitriptyline, doxepin--derivatives of cycloheptadiene as well as imipramine and clomipramine, derivatives of dibenzazepine inhibit the activity of glutathione-S-transferase pi isolated from different regions of human brain (parietal cortex, frontal cortex, brain stem). The inhibitory effect of studied drugs depends more on their chemical structure than on brain localization of the enzyme. All tricyclics bind nonspecifically to the effector site of glutathione-S-transferase (GST).

Characterization of an anti-MUC1 monoclonal antibody with potential as a cancer vaccine.

The monoclonal antibody (MAb) AR20.5 is a murine MAb, generated against the tandem repeat protein backbone of the tumor-associated antigen MUC1. MAb AR20.

Sequencing of new beauverolides by high-performance liquid chromatography and mass spectrometry.

Mass spectrometry (MS) and tandem mass spectrometry (MS(n)) were used for the identification of beauverolides in the fermentation broth of Beauveria bassiana and for evaluation of the purified fraction obtained by sublimation of beauverolides. Besides being a new efficient route for purification of beauverolides, sublimation provided an enrichment of new minor lipophilic beauverolides of lower molecular weight from the original complex mycelial extract. The product ion collision-induced dissociation (CID) spectra obtained on an ion trap (electrospray ionization), the in-source CID mass spectra on a sector instrument (atmospheric-pressure chemical ionization) and the post-source decay matrix-assisted laser desorption/ionization mass spectra of beauverolides were compared and evaluated.

The effect of serotonin, its precursors and metabolites on brain glutathione-S-transferase.

The isoelectric point and substrate specificity of the main isoform of glutathione-S-transferase (GST, EC 2.5.1.

Enzymatic glycosylation using 6-O-acylated sugar donors and acceptors: beta-N-acetylhexosaminidase-catalysed synthesis of 6-O,N,N'-triacetylchitobiose and 6'-O,N,N'-triacetylchitobiose.

p-Nitrophenyl 6-O-acetyl-2-acetamido-2-deoxy-beta-D-glucopyranoside (5a) was used as the glycosyl donor in a beta-N-acetylhexosaminidase-catalysed (from Penicillium brasilianum) glycosylation of GlcNAc yielding 6'-O,N,N'-triacetylchitobiose (6), while 6-O-acetyl-2-acetamido-2-deoxy-beta-D-glucopyranose (3a) served as a selectively protected acceptor in a transglycosylation reaction catalysed by the same enzyme to yield 6-O,N,N'-triacetylchitobiose (4).

The site of oxygen limitation in soybean nodules.

In legume nodules the [O2] in the infected cells limits respiration and nitrogenase activity, becoming more severe if nodules are exposed to subambient O2 levels. To identify the site of O2 limitation, adenylate pools were measured in soybean (Glycine max) nodules that were frozen in liquid N2 before being ground, lyophilized, sonicated, and separated on density gradients of nonaqueous solvents (heptane/tetrachloroethylene) to yield fractions enriched in bacteroid or plant components. In nodules maintained in air, the adenylate energy charge (AEC = [ATP + 0.

The effect of incorporating women's health into a PBL curriculum on students' tendencies to identify learning issues in an ambulatory care setting.

Purpose: To investigate whether the incorporation of women's health into problem-based learning (PBL) cases affects students' tendency to identify learning issues related to women's health as they encounter patients in an ambulatory care setting.

Method: Students in the PBL curriculum at the Allegheny University of the Health Sciences, MCP-Hahnemann School of Medicine, participate in a nine-week primary care practicum at the end of their first year, during which they spend three half-days per week in an ambulatory setting examining patients and completing patient logs that include any learning issues identified. Patient logs from 23 first-year PBL students who had not been exposed to a new women's health education program prior to their practicum in 1993 and from 22 first-year PBL students who had been exposed to the program prior to their practicum in 1994 were reviewed.

Psychiatric screening in primary care: what do patients really want?

Psychiatric disorders are common in primary care, but underdiagnosed. U.S.

Designing evaluations for a women's health education program.

Explicitly incorporating women's health into the medical school curriculum is a relatively new process for educators. Moreover, until recently, no standard definition of women's health had been developed. Because there are no specific evaluation designs for women's health programs, evaluators must adapt existing evaluation concepts to fit the needs of the program.

An antibody-lectin sandwich assay for the determination of CA125 antigen in ovarian cancer patients.

A two-step forward sandwich assay was developed for the determination of the ovarian tumour associated glycoconjugate antigen CA125 with anti-CA125 Monoclonal antibody B27.1 on the solid phase and 125I-labelled wheat germ lectin as tracer in the solution phase. This Mab-lectin heterosandwich assay was optimized and the clinical utility was evaluated in sera from healthy volunteers and ovarian cancer patients.

Primary care patients' reactions to mental health screening.

Objective: The authors examined whether there is empirical support for the notion that medical patients are upset by being asked questions about psychiatric disorders.

Method: Six hundred and one patients attending a primary care clinic completed the SCREENER-a newly developed, brief self-administered questionnaire that surveys a broad range of psychopathology. In addition, they completed a second questionnaire that assessed their attitudes toward the SCREENER.

Psychiatric screening in geriatric primary care: should it be for depression alone?

Depression in the elderly is highly prevalent, associated with functional disability and increased medical costs, and treatable; however, it is infrequently recognized and treated. The Agency for Health Care Policy and Research has advocated, therefore, increased case-finding efforts for depression in primary geriatric care. Anxiety, substance, and somatoform disorders in the elderly are similarly prevalent, associated with disability and cost, treatable, and also infrequently detected and treated.

Effects of Temperature on Infected Cell O2 Concentration and Adenylate Levels in Attached Soybean Nodules.

To assess the role of O2 in the regulation of nodule metabolism following a decrease or an increase in temperature, the fractional oxygenation of leghemoglobin (FOL) was measured in soybean (Glycine max L. Merr.) nodules during rapid and gradual changes in temperature from 20[deg]C to either 15 or 25[deg]C.

Screening for depression in medical patients. Is the focus too narrow?

There is growing consensus that depression is a major public health problem causing significant psychosocial morbidity and mortality which should be addressed by case-finding effects in primary care settings. A large amount of literature has examined the ability of self-report questionnaires to detect depression in medical patients and the results have been encouraging. However, studies of general population and psychiatric patient samples indicate that depression is frequently comorbid with other psychiatric disorders, and that psychiatric disorders other than depression are also associated with significant morbidity and mortality.

Acclimation of Soybean Nodules to Changes in Temperature.

This study examines how O2 status, respiration rate, and nitrogenase activity of soybean (Glycine max) nodules acclimate to short-term (<30 min) temperature change from 20 to 15[deg]C or from 20 to 25[deg]C. Acclimation responses were compared between nodules on uninhibited plants and nodules that were severely O2 limited by exposure to Ar:O2. In uninhibited nodules the decrease in temperature caused a rapid inhibition of nitrogenase activity followed by partial recovery, whereas in Ar:O2-inhibited nodules the temperature decrease caused a minor stimulation followed by a gradual decline in nitrogenase activity.

Screening for psychiatric disorders in medical patients: a feasibility and patient acceptance study.

This study examines whether medical patients were bothered or upset by being asked to complete a questionnaire about emotional and substance use problems, and whether a newly developed, brief questionnaire that screens for several psychiatric disorders (the SCREENER) was easy for patients to complete. A consecutive series of outpatients attending the General Medical Clinic at the Philadelphia Veterans Affair Medical Center (VAMC) was approached to ask their participation in a research study requiring the completion of a brief questionnaire about their emotions, moods, thoughts, and behaviors, and a second questionnaire that asked their opinion about the first measure. Only 3.

Role of Oxygen in the Limitation and Inhibition of Nitrogenase Activity and Respiration Rate in Individual Soybean Nodules.

Although infected cell O2 concentration (Oi) is known to limit respiration and nitrogenase activity in legume nodules, techniques have not been available to measure both processes simultaneously in an individual legume nodule. Consequently, details of the relationship between nitrogenase activity and Oi are not fully appreciated. For the present study, a probe was designed that allowed open circuit measurements of H2 evolution (nitrogenase activity) and CO2 evolution (respiration rate) in a single attached soybean nodule while simultaneously monitoring fractional oxygenation of leghemoglobin (and thereby Oi) with a nodule oximeter.